Signal Transduction Flashcards
What is the name of the transduction pathway where the target cell far from the endocrine cell, and the hormone goes down the blood stream to get to the target?
Endocrine
What is the name of the transduction pathway where the signaling cell secretes signaling molecule that binds to receptor on surface of adjacent cells?
Paracrine
What is the name of the transduction pathway where the binding of neurotransmitters to post-synaptic cell?
Neuronal
What is the name of the transduction pathway where the signaling molecule is transmembrane and binds directly to target cell?
Contact-dependent
What is autocrine signaling?
A cell stimulating itself. The cell has signaling receptors for the same molecule its releasing
What is the definition of signal transduction?
cell converts extracellular signals into intracellular events
cell converts extracellular signals into intracellular events is what?
Signal transduction
How does the same signaling molecule affect different cell types?
They are different affects depending on what the cell type is
Describe how acetylcholine affects heart, salivary, and skeletal muscle cell.
Heart: decreased heart rate
Salivary: secretion
muscle: contraction
The first messenger in the signal transduction pathway is also known as the:
First messenger
Primary messengers bind to _____ on cell surface, and then causes what?
Receptor, conformational change
What is the ultimate goal in signal transduction pathway?
Change in gene expression
What are the two kinds of intracellular signaling proteins?
Kinases & G- proteins
What are G proteins?
GTP binding proteins
To activate kinase, what happens?
phosphorylation
To activate G protein, what happens?
GTP bound
Explain how one small signal can produce a large cell response
The presence of enzymes allow the response to be amplified
What is a role of second messengers in regards to the signal?
It amplifies the signal
Where are you likely to find G-protein coupled receptors?
Adrenergic & olfactory receptors
Where are you likely to find Receptor Tyrosine Kinases?
GFRs, Insulin receptor
Where are you likely to find serine/threonine kinase receptors?
TGFbeta receptor
What are receptors without kinase activity?
Cytokine receptors, integrins
What are ion-channel linked receptors?
neurotransmitters
What are examples of intracellular receptors?
steroid hormone receptors
Ion channels do not have any _____ _____
second messengers
An integrin protein doesn’t have what kind of activity?
kinase
What structural characteristic is important about G protein coupled receptors?
They cross membrane 7 times
A G protein coupled receptor is coupled to what?
A G protein
The G protein in G protein coupled receptors has how many subunits?
3
What does GPCR stand for?
G protein coupled receptor
What subunit on G protein is bound to GPCR?
alpha
Once a ligand binds the receptor what happens to the G protein?
GDP replaced by GTP
Once G protein is replaced with GTP, what is next step?
alpha subunit breaks away and binds to effector
Does the G protein leave the membrane during the signal transduction? Why or why not
No, because it is held onto membrane by fatty acid tail
After the alpha subunit of G protein binds to effector and causes signal, what happens?
alpha unit has GTPase activity and hydrolyses its GTP to GDP then joins the other two subuntis
Name the two main pathways we have to know for GPCR & G protein pathways
- Creates cAMP as 2nd messenger
(effector protein= adenyl cyclase) - Creates DAG & IP3 as 2nd messengers
(effector protein= phospholipase C; PLC)
Describe the signaling pathway (all the steps) with G protein where cAMP is second messenger
(ppt# 17)
signal molecule ginds to GPCR → G protein exchanges GDP for GTP → G protein activates adenylyl cyclase → Adenylyl cyclase converts ATP to cAMP → cAMP activates PKA (protein kinase A) →PKA phosphorylates other proteins → cellular response
What two amino acids are part of PKA?
Serine & Threonine
What does CRE stand?
cAMP response element
What does CRE do?
region within promoter that genes that respond to cAMP have
What does cAMP specifically bind to in signal pathway?
regulatory unit of PKA
The PKA activates catalytic proteins, and it also does what?
Goes into nucleus and activates TFs
What does CREB stand for?
cAMP response element binding protein
What does CREB do?
initiates transcription activity
Describe the steps once PKA enters nucleus
PKA enters nucleus → phosphorylates TFs → CREB binds to promoter region on CRE → gene activity
What inactivates or blocks cAMP activity?
cAMP phosphodiesterase & caffeine
What does Gs stand for?
Stimulatory G protein
What does Gi stand for?
Inhibitory G protein
What does Gi protein do?
Same mechanism as Gs protein, like in cAMP activation, but it would inhibit the effect
The cholera toxin, E. coli toxin, pertussis toxin all do what?
Lock G protein
What is ADP ribosylation?
The change that occurs to lock G protein in its state
Explain what happens in the cholera and E.coli toxin with G protein
Gs locked in GTP bound state - very high levels of cAMP
Explain what happens w/ pertussis toxin and G protein
Gi locked in GDP bound - very high levels of cAMP
Describe the signaling pathway (all the steps) of G protein where DAG & IP3 are second messengers
Signal molecule binds to GPCR → G protein (Gq protein) GDP to GTP → activates PCL → breaks down inositol phospholipid into two second messengers: IP3 & DAG → IP3 binds calcium ion channel on sER → calcium release → DAG and IP3 both activate PKC → PKC activates transcription factors
What does PLC stand for?
phospholipase C
What does PLC stand for?
phospholipase C
What does IP3 stand for?
Inositol, 1,4,5-triphosphate
Key word: Rhodopsin
Retinitis pigmentosa 4
Characteristics: Loss/diminished night and peripheral vision; Treatment: Vitamin A slows progression is what disease?
Retinitis pigmentosa 4
What is the mechanism for retinitis pigmentosa 3?
Mutation of Rhodopsin (GPCR) causes degeneration of photoreceptor cells in the retina
What does RTK stand for?
Receptor Tyrosine Kinase
Most growth factors are what kind of kinase?
RTK
Name three domains in RTK
transmembrane domain, lingand binidng domain, tyrosine kinase domain on inside
How are RTK activated?
ligand binds and then they dimerize
Describe the general steps in TK signaling pathway
Ligand binds → Receptor dimerization → tyrosine phosphorylation → kinase activation → phosphorylation effector proteins
What does TK stand for?
Tyrosine Kinase
RTK always function as ___
dimers
What is the purpose of the Pl3K pathway?
Cell survival
List the steps of the Pl3K pathway
Signal binds RTK→ dimerization → RTK phosphorylate each other → RTK phosphorylates Pl3K → Pl3K phosphorylates PIP2 → PIP3 → PIP3 activates AKT → phosphorylates BAD → inhibition of apoptosis
What is another name for Akt?
PKB
What is BAD?
pore forming, pro-apoptosis protein
What happens when BAD is phosphorylated?
It is inactivated
What does PKB inhibit?
BAD
What does BAD inhibit?
BCL-2
What does BCL-2 inhibit?
BAX
What does BAX do?
form pores
What protein is actually forming the pores for apoptosis?
BAX
What G protein pathway is the same for RTK pathway?
IP3 & DAG messengers
What are the domains of Grb2?
SH2 & two SH3 domains
What domain of Grb2 binds to RTK?
SH2 domain
What does SH3 domain of Grb2 bind to?
Ras-GEF
What is another name for Ras-GEF
Sos
What are the steps in the Ras-MAPK pathway?
signal protein binds RTK → dimerization → autophosphorylation → autophosphorylation makes binding sites for signaling proteins → SH2 domain of Grb2 binds → SH3 domain of Grb2 binds to Ras-Gef → Ras-Gef activates Ras protein (GDP→GTP) → activates Raf → phosphorylates Mek → phosphorylates Map K (Erk) → TFs → change gene expression and protein activity
Insulin receptor is a ____ ____
tyrosine kinase
Key words: hyperglycemia, obesity, insulin resistance are what disease?
NIDDM (Non Insulin-Dependent Diabetes Mellitis)
What does NIDDM stand for?
NIDDM (Non Insulin-Dependent Diabetes Mellitis)
Characteristics: #1 risk factor - obesity are what disease?
NIDDM
What is the mechanism for NIDDM?
Hyperglycemia → affects blood vessels, kidneys, eyes, nerves; Insulin resistance in skeletal muscle, liver, & adipose tissue due to down regulation of insulin receptor → decreased receptor phosphorylation & TK activity → decreased 2nd messengers in pathway; Pancreatic B-cell dysfunction ! insulin deficiency
Over activation of RTK can cause ______
cancer
EGFR (HER1) is what cancer?
Breast
EGFR2 (HER2) is what cancer?
breast
VEGF is what cancer?
colorectal cancer, NSCLC
What are cytokine receptors?
No enzymatic activity - they are like RTKs but no enzymatic activity
What associates with cytokine receptors but is not a part of the cytokine itself?
kinase
What are the two receptors without kinase activity?
cytokine receptors, integrin receptors
Explain the Jak/STAT pathway
Cytokine binds to cytokine receptors → dimerization → JAK (a kinase associated w/ cytokine) phosphorylates each other → JAK phosphorylates cytokine receptor → STAT binds to cytokine receptor → STAT phosphorylated by JAK → STAT active → activated STATs dimerize and migrate to nucleus → gene regulation
What does ILK stand for?
Integrin-linked kinase
What does FAK stand for?
Focal adhesion kinase
Describe what I should know about integrin receptor pathway
integrin receptors heterodimerize and bind to ECM proteins, receptors @ bottom of integrin associate with kinases,
What is an integrin receptor?
Ligand binding →clustering of receptors which recruits & activates kinases
What two kinases might integrin receptors link with?
ILK or FAK
Describe ion channel linked receptors
Ligand binding → conformational change → gate opens → influx of ions (often Ca2+)
How neurons work
All hormone receptors are ____ ___
transcription factors
Where are hormone receptors found?
cytoplasm & nucleus
Steroid hormone receptors all have what two domains?
DNA binding domain & hormone binding domain
Describe steroid hormone pathway
Steroid hormone diffuse membrane → bind receptor → conformational change/dimerization → translocation to nucleus → TFs
Where do steroid hormone receptors bind to in DNA?
HRE - Hormone response element
What does HRE stand for?
Hormone response element
Grb2 is NOT what?
an enzyme - it acts as an anchor for Ras-GEF
What is a prominent adaptor protein involved in RTK signaling?
Grb2
